Markers of nutritional status and inflammation in transthyretin cardiac amyloidosis: association with outcomes and the clinical phenotype

Abstract

Background: Patients with transthyretin (TTR) cardiac amyloidosis demonstrate cardiac cachexia with progression of their cardiomyopathy, which is characterised by malnutrition and a heightened inflammatory state. How best to measure this condition is less well characterised. We investigated differences in survival among patients with ATTR cardiac amyloidosis by nutritional status as defined by modified BMI (mBMI) and by inflammatory state as defined by serum uric acid.

Methods and results: This study was a retrospective analysis of patients diagnosed with ATTR cardiac amyloidosis at a single tertiary medical centre. Baseline characteristics were compared by nutritional status as measured by mBMI and by inflammatory state as measured by serum uric acid. Kaplan-Meier survival analyses were used to compare nutritional status and inflammatory status for the composite outcome of death. Cox proportional hazards modelling was used to assess predictors of death in this cohort. Three hundred patients (mean age 75 ± 11) years, 84.3% male) were included. Those with low mBMI (<1185 kg/m² g/L) had shorter time to death (5.4 vs. 6.8 years, log rank p = .045) and those with elevated serum uric acid (>8.8 mg/dL) had shorter time to death (4.9 vs. 7.7 years, log rank p < .0001). Those with both low mBMI and elevated serum uric acid had the shortest time to death (4.3 years, log rank p = .005). In this cohort, mBMI was not a univariate predictor of death though there was a trend towards significance (HR 0.92, per 100 kg/m² g/L, 95% CI 0.828–1.016, p = .099). Serum uric acid was a univariate predictor of death (HR 1.27 per 1 mg/dL, 95% CI 1.114–1.455, p < .001). In multivariate Cox analysis, this association remained significant (HR 1.31 per 1 mg/dL increase, 95% CI 1.096–1.560, p = .003) as well as in a separate stepwise model controlling for potential confounders including daily diuretic use, uric acid lowering therapy, and renal dysfunction.

Conclusions: Both nutritional status as measured by mBMI and inflammation as measured by serum uric acid are associated with survival in patients with TTR cardiac amyloidosis however only serum uric acid is an independent predictor of death.

Keywords:

• Transthyretin
• cardiac
• amyloidosis
• nutrition
• inflammation

Disclosure statement

Dr. Maurer’s institution received research support for clinical studies from Pfizer and Alnylam. He has served on advisory boards or data safety and monitoring boards for Ackea, Ionis, Prothena, Pfizer, Alnyam, Eidos and GSK. The other authors report no conflict of interest.

Additional information

Funding

Dr. Maurer is funded by K24-AG036778 from the National Institute on Aging. This study was also funded by an 5R21AG058348 from NIA.